Abstract

Dopamine (DA) contained in the dense network of DA fibers innervating the striatum has been shown to play a major role in the regulation of striatal neuron activity. This has been approached by analyzing either changes in electrophysiological properties of neurons (Bernardi et al., 1978; Calabresi et al., 1988) or changes in biochemical parameters such as the levels and/or the synthesis (Hong et al., 1978a and b; Hanson et al., 1988; Li et al., 1987) or the release (Lehman and Langer, 1983; Girault et al., 1986a) of specific neurotransmitters localized in striatal neurons. A useful tool in understanding the regulation of neuronal activity is now offered by molecular biology which allows the identification of specific mRNAs, reflecting earlier events than neurotransmitter contents. In this study, we tried to elucidate the DA receptor subtype which mediates dopaminergic modulation of the expression of messengers encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE), two major markers contained in projection neurons of the striatum (Fonnum et al., 1974; Cuello et al. 1978). This analysis has been initiated by previous findings showing that a 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal DA neurons produced increased levels of mRNAs encoding GAD (Vernier et al., 1988) and PPE (Angulo et al. 1986; Young et al., 1986; Normand et al. 1988), and that these effects could be reproduced by chronic treatments with haloperidol (Sabol et al., 1983; Tang et al., 1983; Sivam et al., 1986; Normand et al., 1987; Morris et al., 1988; Vernier unpublished observations). These previous studies suggested an inhibitory control of DA on the expression of both GAD- and PPE-mRNA. The action of DA being mediated by an interaction with at least two receptor subtypes, coupled to different second messenger systems (Stoof and Kebabian, 1981), it was of interest to elucidate the receptor subtype involved in these effects.